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Study Seeks Biomarkers for Invisible War Scars

Dr. Charles R. Marmar, chairman of the psychiatry department at NYU Langone Medical Center, is leading a study on PTSD.Credit
Richard Perry/The New York Times

Over the past decade, about half a million veterans have received diagnoses of post-traumatic stress disorder or traumatic brain injury. Thousands have received both. Yet underlying the growing numbers lies a disconcerting question: How many of those diagnoses are definitive? And how many more have been missed?

No one can say. Though PTSD is hardly new, diagnoses still largely rely on self-reported symptoms. And while severe brain injuries are often clearly diagnosable, finding evidence of mild T.B.I.’s, particularly older ones, can be all but impossible.

It means that for a soldier who, five years after duty in Iraq, still feels “not right,” with symptoms from headaches to sleeping problems to irritability, doctors can only guess at the cause. Maybe PTSD. Maybe T.B.I. Maybe both.

Now, in one of the largest studies of its kind, a team of researchers based out of New York University’s medical school have begun a five-year study to find biological signals, known as biomarkers, that could provide reliable, objective evidence of those so-called invisible injuries of war.

“We want to elevate mental health to standard physical health,” said Dr. Charles R. Marmar, chairman of the psychiatry department at NYU Langone Medical Center, and the lead investigator on the project.

“You don’t go from having shortness of breath to having cardiac surgery; you have a series of objective lab tests first,” he said. “We would like to do the same thing with PTSD and T.B.I. That is, go beyond subjective reports.”

Dr. Marmar faces deep skepticism that biological signals can be found for psychiatric disorders like PTSD or depression, which his group is also studying, or even a less severe brain injury.

But while previous quests have failed to produce results that could be replicated, private foundations and the government still seem willing to finance new efforts, amid the growing tally of disabled veterans.

Researchers at the Uniformed Services University of the Health Sciences, the military’s medical school in Bethesda, Md., are studying soldiers at Fort Bragg, N.C., in search of PTSD biomarkers. And Draper Laboratory, a nonprofit research company based in Cambridge, Mass., has recruited experts to look for biomarkers for the disorder.

Dr. Marmar’s project is significant both because of its size — researchers hope to recruit 1,500 subjects — but also because much of its financing is already guaranteed through a $17 million grant from the Steven A. and Alexandra M. Cohen Foundation, founded by the billionaire hedge-fund manager. Dr. Marmar hopes to match that with federal grants.

Biomarkers are physiological road signs that can tell doctors whether a person has a disease or injury, or is likely to contract a particular ailment. Tissue damaged by a heart attack releases chemicals into the blood that can be detected. Abnormal levels of the proteins amyloid and tau, as well as shrinkage of certain areas of the brain, are considered markers of Alzheimer’s disease.

The lack of reliable markers for PTSD and mild T.B.I. has had significant consequences, experts say. Without clear-cut tests to spot them early, the disorders can go undetected until symptoms become disabling. Misdiagnoses readily occur, leading to ineffective or even damaging treatments. And because diagnoses rely heavily on self-reported symptoms, weeding out fraudulent claims for disability benefits can be difficult and contentious.

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Dr. Marmar said a long-term goal is to use marker research to develop inexpensive tests for PTSD and T.B.I. — ideally, he said, like home pregnancy tests.

The study plans to look at five groups, each consisting of 300 veterans: people with PTSD; with T.B.I.; with both; and with depression but without PTSD or T.B.I. The fifth group will comprise veterans with combat deployments who show no symptoms of any of those disorders.

The subjects will undergo a diverse battery of tests to analyze hormone levels, blood chemistry, genetic makeup, brain structure and even voices.

One team will use magnetic resonance imaging to compare the brain structures of healthy people with those of people with PTSD. Preliminary data suggests that people with the disorder may have detectable damage in areas of the brain involved in processing memories and in regulating emotions like fear or arousal, said Dr. Michael Weiner, a professor of radiology at the University of California, San Francisco, who will assist in image analysis.

Another team will use brain imaging to test a theory that abnormalities in the thalamus, a part of the central brain that acts as a switchboard for nerve signals, are an indication of head trauma, said Dr. Robert I. Grossman, dean and chief executive of the Langone Medical Center and a senior adviser on the study.

“We’ve seen this in 25 to 30 patients,” Dr. Grossman said. “But you need hundreds of patients to validate the hypothesis. That’s the beauty of this project.”

Other researchers will look for biomarkers in genes, blood and hormones. One group will even analyze audio recordings of speech to see whether evidence of PTSD can be found in the pitch, timber and tone of voices.

Bruce Knoth, a software engineer with SRI International, a research institute based in Northern California that is working with Dr. Marmar, said those recordings would be run through software that extracts scores of features in each voice. They will search for patterns in the voices of veterans with PTSD or T.B.I., then compare those with the voices of healthy people.

The technique, based on the notion that voices are as unique as fingerprints, is in its infancy. Mr. Knoth said similar research is being used to try to identify markers for suicidal behavior.

Though scientists have made some strides in identifying biomarkers for T.B.I., there has been minimal progress in identifying them for PTSD or depression, and many mental health experts believe the search is futile.

But Dr. Marmar asserted that recent advances in genetic research and brain imaging have provided powerful new tools for studying the structure and functioning of the nervous system — without invasive procedures.

“We’re at the beginning, it’s true,” he said. “We should be like cardiologists, able to test biologically for mental health problems. The difficulty is that while the heart is a pump, the brain is 100 orders more complicated.”

A version of this article appears in print on February 7, 2013, on Page A17 of the New York edition with the headline: Study Seeks Biomarkers For Invisible War Scars. Order Reprints|Today's Paper|Subscribe